The purpose of the proposed investigation is to demonstrate an association of virus infection with the development and progression of chronic renal disease. In considering candidate etiologic agents as causes of chronic glomerulonephritis, clinical observation, animal modes, and an increasing body of knowledge concerning latent and persistent human viruses serve as precedents for implicating viruses as potential causes of human renal disease. The proposed investigation will take five approaches: (1) Immunofluorescence for viral antigen -all renal biopsies showing an immune-complex pattern of staining for immunoglobulin will be further evaluated by indirect immunofluorescence for various viral antigens. (2) Serologic survey: Using microtitration techniques, antibody titers against paramyxo and myxovirus and hepatitis-B antigen and EB virus will be determined in patients with acute and chronic renal diseases. Data including appropriate controls will be computer analyzed. (3) Antibody elution and titration from "end-stage" kidneys: Kidneys removed prior to renal transplantation will be examined by immunofluorescence. Antibody will be eluted from immunofluorescent-positive kidneys, and the resultant antibody product titered by microtitration in an attempt to identify viral specificity. (4) Long-term cultivation of kidneys in tissue culture: Samples of whole kidneys from patients undergoing renal transplantation will be established in long-term tissue culture in an attempt to isolate a candidate virus. Using well established tissue culture methods, "virus rescue" will be attempted and monitored by electron microscopy. (5) Animal model: Murine cytomegalovirus (MCMV)-induced glomerulonephritis in the mouse will be further studied in an attempt to demonstrate persistence of viral antigen and possible development of chronic renal disease. Mice persistently infected with MCMV will be chronically immuno-suppressed with anti-lymphocyte serum in an attempt to induce a chronic viral glomerulonephritis. Other animal models of renal disease will be considered for potential inclusion in this project.